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. 1962 Oct 31;116(5):719–738. doi: 10.1084/jem.116.5.719

GENETIC CHARACTERS OF HUMAN γ-GLOBULINS IN MYELOMA PROTEINS

M Harboe 1, C K Osterland 1, M Mannik 1, H G Kunkel 1
PMCID: PMC2137565  PMID: 13952722

Abstract

The genetic factors Gm(a), Gm(b), Gm(x), and Inv(a), Inv(b) described for normal human γ-globulin were all found in different myeloma proteins. A single myeloma protein never contained more than one product of alternate alleles even in heterozygous individuals. However, factors determined by the two different loci were often found in the same myeloma protein. The Gm(a) character of the myeloma protein parallelled that of the normal γ-globulin of the same serum in most cases. In contrast, the Gm(b) character was usually absent in the myeloma protein when it was directly demonstrable in the normal γ-globulin. The myeloma proteins from six Negroes were Gm(a+b-), whereas the normal γ-globulin was Gm(a+b+). This indicates that the effect of gene Gm b is similar in Negroes and whites, even though its relation to gene Gm a is different in the two races. Gm factors were found only in the 7S γ-globulin type myelomas and not in other products of plasma cell tumors. Inv characters were, however, present in all four types of proteins studied, namely 7S and 19S γ-globulins, β2A-globulins, and Bence Jones proteins. In two instances, genetic heterogeneity of the protein products was demonstrated suggesting the proliferation of more than one clone of plasma cells in some multiple myeloma patients. The accumulated evidence obtained in this study strongly suggested that the presence and absence of genetic characters was compatible with the concept that myeloma proteins were closely analogous to individual moieties in the spectrum of normal γ-globulins rather than truly abnormal proteins. Their study offered evidence of a heterogeneity of genetic characters among the normal γ-globulins in a given individual. It also appears probable that in normal individuals single plasma cells have a restricted capacity to express genetic information in their protein product.

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Selected References

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  1. ASKONAS B. A. A study on globulin formation by plasma-cell neoplasm (5563) transplantable in mice. Biochem J. 1961 Apr;79:33–43. doi: 10.1042/bj0790033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ASKONAS B. A., FAHEY J. L. Enzymatically produced subunits of proteins formed by plasma cells in mice. II. beta2a-Myeloma protein and Bence Jones protein. J Exp Med. 1962 Mar 1;115:641–653. doi: 10.1084/jem.115.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DEUTSCH H. F., KRATOCHVIL C. H., REIF A. E. Immunochemical relation of Bence-Jones proteins to normal serum proteins. J Biol Chem. 1955 Sep;216(1):103–111. [PubMed] [Google Scholar]
  4. EDELMAN G. M., BENACERRAF B. On structural and functional relations between antibodies and proteins of the gamma-system. Proc Natl Acad Sci U S A. 1962 Jun 15;48:1035–1042. doi: 10.1073/pnas.48.6.1035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. EDELMAN G. M., GALLY J. A. The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins. J Exp Med. 1962 Aug 1;116:207–227. doi: 10.1084/jem.116.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. EDELMAN G. M., HEREMANS J. F., HEREMANS M. T., KUNKEL H. G. Immunological studies of human gamma-globulin. Relation of the precipitin lines of whole gamma-globulin to those of the fragments produced by papain. J Exp Med. 1960 Jul 1;112:203–223. doi: 10.1084/jem.112.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. EDELMAN G. M., POULIK M. D. Studies on structural units of the gamma-globulins. J Exp Med. 1961 May 1;113:861–884. doi: 10.1084/jem.113.5.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. FAHEY J. L., ASKONAS B. A. Enzymatically produced subunits of proteins formed by plasma cells in mice. I. gamma-Globulin and gamma-myeloma proteins. J Exp Med. 1962 Mar 1;115:623–639. doi: 10.1084/jem.115.3.623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. FAHEY J. L., LAWLER S. D. Gm factors in normal gamma-globulin fractions, myeloma proteins, and macroglobulins. J Natl Cancer Inst. 1961 Nov;27:973–981. [PubMed] [Google Scholar]
  10. FAHEY J. L. Physiocochemical characterization of mouse myeloma proteins: demonstration of heterogeneity for each myeloma globulin. J Exp Med. 1961 Sep 1;114:399–413. doi: 10.1084/jem.114.3.399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FRANKLIN E. C., FUDENBERG H., MELTZER M., STANWORTH D. R. The structural basis for genetic variations of normal human gamma-globulins. Proc Natl Acad Sci U S A. 1962 Jun 15;48:914–922. doi: 10.1073/pnas.48.6.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. FRANKLIN E. C. Structural units of human 7S gamma globulin. J Clin Invest. 1960 Dec;39:1933–1941. doi: 10.1172/JCI104218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Franklin E. C., Stanworth D. R. ANTIGENIC RELATIONSHIPS BETWEEN IMMUNE GLOBULINS AND CERTAIN RELATED PARAPROTEINS IN MAN. J Exp Med. 1961 Sep 30;114(4):521–533. doi: 10.1084/jem.114.4.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. GRUBB R., LAURELL A. B. Hereditary serological human serum groups. Acta Pathol Microbiol Scand. 1956;39(6):390–398. doi: 10.1111/j.1699-0463.1956.tb05067.x. [DOI] [PubMed] [Google Scholar]
  15. HARBOE M., LUNDEVALL J. A new type in the Gm system. Acta Pathol Microbiol Scand. 1959;45(4):357–370. doi: 10.1111/j.1699-0463.1959.tb04721.x. [DOI] [PubMed] [Google Scholar]
  16. HARBOE M., OSTERLAND C. K., KUNKEL H. G. Localization of two genetic factors to different areas of gamma-globulin molecules. Science. 1962 Jun 15;136(3520):979–980. doi: 10.1126/science.136.3520.979. [DOI] [PubMed] [Google Scholar]
  17. HARBOE M. Quantitative studies on the hemagglutination inhibition reaction for determination of the Gm types. Acta Pathol Microbiol Scand. 1959;47:199–208. doi: 10.1111/j.1699-0463.1959.tb04849.x. [DOI] [PubMed] [Google Scholar]
  18. HEREMANS J. F., HEREMANS M. T., SCHULTZE H. E. Isolation and description of a few properties of the beta 2A-globulin of human serum. Clin Chim Acta. 1959 Jan;4(1):96–102. doi: 10.1016/0009-8981(59)90088-9. [DOI] [PubMed] [Google Scholar]
  19. KORNGOLD L., LIPARI R. Multiple-myeloma proteins. I. Immunological studies. Cancer. 1956 Jan-Feb;9(1):183–192. doi: 10.1002/1097-0142(195601/02)9:1<183::aid-cncr2820090119>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  20. KORNGOLD L., LIPARI R. Multiple-myeloma proteins. III. The antigenic relationship of Bence Jones proteins to normal gammaglobulin and multiple-myeloma serum proteins. Cancer. 1956 Mar-Apr;9(2):262–272. doi: 10.1002/1097-0142(195603/04)9:2<262::aid-cncr2820090210>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  21. KUNKEL H. G., FUDENBERG H., OVARY Z. High molecular weight antibodies. Ann N Y Acad Sci. 1960 Jun 30;86:966–973. doi: 10.1111/j.1749-6632.1960.tb42853.x. [DOI] [PubMed] [Google Scholar]
  22. KUNKEL H. G., SLATER R. J., GOOD R. A. Relation between certain myeloma proteins and normal gamma globulin. Proc Soc Exp Biol Med. 1951 Jan;76(1):190–193. doi: 10.3181/00379727-76-18432. [DOI] [PubMed] [Google Scholar]
  23. KUNKEL H. G. Zone electrophoresis. Methods Biochem Anal. 1954;1:141–170. doi: 10.1002/9780470110171.ch6. [DOI] [PubMed] [Google Scholar]
  24. MORSE J. H., HEREMANS J. F. Immunoelectrophoretic analysis of human insulin-binding antibody and its papain-produced fragments. J Lab Clin Med. 1962 Jun;59:891–897. [PubMed] [Google Scholar]
  25. OSSERMAN E. F. Plasma-cell myeloma. II. Clinical aspects. N Engl J Med. 1959 Nov 5;261:952–cont'd. doi: 10.1056/NEJM195911052611906. [DOI] [PubMed] [Google Scholar]
  26. OUDIN J. Allotypy of rabbit serum proteins. I. Immuno-chemical analysis leading to the individualization of seven main allotypes. J Exp Med. 1960 Jul 1;112:107–124. doi: 10.1084/jem.112.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. POTTER M., KUFF E. L. Myeloma globulins of plasma-cell neoplasms in inbred mice. I. Immunoelectrophoresis of serum, with rabbit antibodies prepared against microsome fractions of the neoplasms. J Natl Cancer Inst. 1961 May;26:1109–1137. [PubMed] [Google Scholar]
  28. POTTER M. Plasma cell neoplasia in a single host: a mosaic of different protein-producing cell types. J Exp Med. 1962 Feb 1;115:339–356. doi: 10.1084/jem.115.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. ROPARTZ C., LENOIR J., RIVAT L. A new inheritable property of human sera: the InV factor. Nature. 1961 Feb 18;189:586–586. doi: 10.1038/189586a0. [DOI] [PubMed] [Google Scholar]
  30. ROPARTZ C., ROUSSEAU P. Y., RIVAT L., LENOIR J. [Genetic study of the In-v serum factor. Incidence in certain populations]. Rev Fr Etud Clin Biol. 1961 Apr;6:374–377. [PubMed] [Google Scholar]
  31. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  32. SLATER R. J., WARD S. M., KUNKEL H. G. Immunological relationships among the myeloma proteins. J Exp Med. 1955 Jan 1;101(1):85–108. doi: 10.1084/jem.101.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. STEINBERG A. G., GILES B. D., STAUFFER R. A Gm-like factor present in Negroes and rare or absent in whites: its relation to Gma and Gmx. Am J Hum Genet. 1960 Mar;12:44–51. [PMC free article] [PubMed] [Google Scholar]

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